A One-Pot O-Phosphinative Passerini/Pudovik Reaction: Efficient Synthesis of Highly Functionalized α-(Phosphinyloxy) amide Derivatives

A one-pot O-phosphinative Passerini/Pudovik reaction has been developed, based on reacting aldehydes, isocyanides, and phosphinic acids followed by the addition of second aldehydes to form the corresponding -(phosphinyloxy)amide derivatives. This is the first reported instance of a Passerini-type, isocyanide-based multicomponent reaction using a phosphinic acid instead of a carboxylic acid. The nucleophilicity of the phosphinate group allows a subsequent catalytic Pudovik-type reaction, affording the highly functionalized -(phosphinyloxy)amide derivative in high yield. A wide range of aldehydes and isocyanides are applicable to this reaction.